1,2-Dichloroethane → HCID 25066830, compound

HRID 1919602Notes

Reaction equation

HRID 1919602 reaction equation
[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:25](O)=[O:26])[CH:23]=3)[NH:18][CH:17]=2)=[N:6][C:5]=1[CH3:28])(=[O:3])[CH3:2].FC1C(O)=C(F)C(F)=C(F)C=1F.C[CH2:42][N:43](C(C)C)[CH:44](C)C.C(Cl)CCl.CNC>CN(C=O)C>[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:25]([N:43]([CH3:44])[CH3:42])=[O:26])[CH:23]=3)[NH:18][CH:17]=2)=[N:6][C:5]=1[CH3:28])(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 674DimethylamineHCID 13041PentafluorophenolHCID 81531DiisopropylethylamineHCID 25066829HCID 25066829, compound

Product 1

HCID 25066830HCID 25066830, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of Example 11 (0.115 g, 0.29 mmol) in DMF (2 mL) was added pentafluorophenol (0.064 g, 0.35 mmol), DIPEA (0.100 mL, 0.57 mmol) and EDC (0.072 g, 0.37 mmol). The reaction mixture was stirred at r.t. for 48 h. Dimethylamine (40% w/v in water, 5 mL) was added and the reaction mixture stirred for 16 h at r.t. The reaction mixture was concentrated in vacuo. DCM (5 mL) and water (5 mL) were added. The aqueous layer was extracted with DCM (2×3 mL). The combined organic fractions were washed with water (3×15 mL), dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (0.040 g, 45%) as a white solid. δH (CD3OD) 8.07 (1H, s), 7.42 (1H, m), 7.25-7.19 (2H, m), 4.39-4.29 (1H, m), 4.14-3.99 (1H, m), 3.88 (1H, d, J 11.9 Hz), 3.72-3.51 (4H, m), 3.42 (1H, dd, J 13.8 Hz and J 10.2 Hz), 3.19-3.03 (7H, m), 2.57 (3H, s), 2.43 (3H, s). Exchangeable proton not observed. LCMS (ES+) 427.0 (M+H)+, RT 2.59 minutes (Method 2).

Workup

  1. stirringthe reaction mixture stirred for 16 h at r.t
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionDCM (5 mL) and water (5 mL) were added
  4. extractionThe aqueous layer was extracted with DCM (2×3 mL)
  5. washThe combined organic fractions were washed with water (3×15 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo
  9. customThe residue was purified by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-e519237a9bce4069850f3182391c715a
Source dataset
uspto-grants-2012_05
Patent number
US08168634B2

Reaction notes

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